Underivatized, aqueous soluble .beta.(1-3)-glucan (also known as PGG-Glucan or Betafectin.RTM.) is a novel and unique soluble .beta.-glucan manufactured through a proprietary process. The biological activity of this molecule is clearly distinguishable from particulate or other soluble .beta.-glucans. Numerous laboratories have reported direct induction of arachidonic acid metabolites (Czop et al., J. Immunol. 141(9):3170-3176 (1988)), cytokines (Abel and Czop, Intl. J. Immunopharmacol. 14(8):1363-1373 (1992); Doita et al., J. Leuk. Biol. 14(2):173-183 (1991)) and oxidative burst (Cain et al., Complement 4:75-86 (1987); Gallin et al., Int. J. Immunopharmacol. 14(2):173-183 (1992)) by both particulate and soluble forms of .beta.-glucans. In contrast, underivatized, aqueous soluble .beta.(1-3)-glucan does not directly activate leukocyte functions such as oxidative burst activity (Mackin et al., FASEB J. 8:A216 (1994)), cytokine secretion (Putsiaka et al.,Blood 82:3695-3700 (1993)) or proliferation (Wakshull et al., J. Cell. Biochem. suppl. 18A:22 (1994)). Instead, underivatized, aqueous soluble .beta.(1-3)-glucan primes cells for activation by secondary stimuli (Mackin et al. (1994); Brunke-Reese and Mackin, FASEB J. 8:A488 (1994); and Wakshull et al. (1994)).
The biological activity of .beta.-glucans is mediated through specific receptors located on target cells. Several groups of investigators have described receptors which bind particulate .beta.-glucan preparations. For example, receptors for particulate .beta.-glucans (e.g., zymosan-like particles) have been described by Czop and colleagues (Czop and Kay, J. Exp. Med. 173:1511-1520 (1991); Szabo et al., J. Biol. Chem. 270:2145-2151 (1995)) and Goldman (Immunology 63(2):319-324 (1988); Exp. Cell. Res. 174(2):481-490 (1988)). The leukocyte complement receptor 3 (CR3, also known as MAC 1 or CD11b/CD18) has been shown to have the capacity to bind both particulate and some soluble .beta.-glucans, as well as other polysaccharides (Thornton et al., J. Immunol. 156:1235-1246 (1996)). A soluble aminated .beta.-glucan preparation has been shown to bind to murine peritoneal macrophages (Konopski et al., Biochim. Biophys. Acta 1221:61-65 (1994)), and a phosphorylated .beta.-glucan derivative has been reported to bind to monocyte cell lines (Muller et al., J. Immunol. 156:3418-3425 (1996)). The ability of salmon macrophages (Engstad and Robertsen, Dev. Comp. Immunol. 18(5):397-408 (1994)) and brain microglial cells (Muller et al., Res. Immunol. 145:267-275 (1994)) to phagocytose .beta.-glucan particles, presumably through a receptor-mediated process, has also been described.
Unfortunately, each group has utilized .beta.-glucan preparations varying widely in their source, method of preparation, purity and characterization. In addition, different cell types and species, both primary and established cell lines, and different functional read-outs have been used. The relationship between the various receptors described by these investigators has, therefore, not been defined, although it is clear that the receptor described by Czop is not CR3 (Szabo et al. (1995)).